Longitudinal Intravascular Antibody Labeling Identified Regulatory T Cell Recruitment as a Therapeutic Target in a Mouse Model of Lung Cancer

Authors

Sean-Luc Shanahan
Nikesh Kunder
Charles Inaku
Natalie B Hagan
Grace Gibbons
Nicolas Mathey-Andrews
Gayathri Anandappa
Shawn Soares
Kristen E Pauken
Tyler Jacks
Jason M Schenkel

Language

English

Publication Date

9-15-2024

Journal

Journal of Immunology

DOI

10.4049/jimmunol.2400268

PMID

39082930

PMCID

PMC11460633

PubMedCentral® Posted Date

9-15-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Anticancer immunity is predicated on leukocyte migration into tumors. Once recruited, leukocytes undergo substantial reprogramming to adapt to the tumor microenvironment. A major challenge in the field is distinguishing recently recruited from resident leukocytes in tumors. In this study, we developed an intravascular Ab technique to label circulating mouse leukocytes before they migrate to tissues, providing unprecedented insight into the kinetics of recruitment. This approach unveiled the substantial role of leukocyte migration in tumor progression using a preclinical mouse model of lung adenocarcinoma. Regulatory T cells (Tregs), critical mediators of immunosuppression, were continuously and rapidly recruited into tumors throughout cancer progression. Moreover, leukocyte trafficking depended on the integrins CD11a/CD49d, and CD11a/CD49d blockade led to significant tumor burden reduction in mice. Importantly, preventing circulating Treg recruitment through depletion or sequestration in lymph nodes was sufficient to decrease tumor burden, indicating that Treg migration was crucial for suppressing antitumor immunity. These findings underscore the dynamic nature of the immune compartment within mouse lung tumors and demonstrate the relevance of a temporal map of leukocyte recruitment into tumors, thereby advancing our understanding of leukocyte migration in the context of tumor development.

Keywords

Animals, T-Lymphocytes, Regulatory, Mice, Lung Neoplasms, Disease Models, Animal, Cell Movement, Mice, Inbred C57BL, Tumor Microenvironment, Adenocarcinoma, Cell Line, Tumor, T cells, Leukocyte trafficking, Tregs in tumors, migration tracking, systemic immunity

Published Open-Access

yes

Recommended Citation

Shanahan, Sean-Luc; Kunder, Nikesh; Inaku, Charles; et al., "Longitudinal Intravascular Antibody Labeling Identified Regulatory T Cell Recruitment as a Therapeutic Target in a Mouse Model of Lung Cancer" (2024). Faculty, Staff and Student Publications. 6397.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6397